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Corti F, Rossi RE, Cafaro P, Passarella G, Turla A, Pusceddu S, Coppa J, Oldani S, Guidi A, Longarini R, Cortinovis DL. Emerging Treatment Options for Neuroendocrine Neoplasms of Unknown Primary Origin: Current Evidence and Future Perspectives. Cancers (Basel) 2024; 16:2025. [PMID: 38893145 PMCID: PMC11171242 DOI: 10.3390/cancers16112025] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/25/2024] [Revised: 05/19/2024] [Accepted: 05/22/2024] [Indexed: 06/21/2024] Open
Abstract
Among neuroendocrine neoplasms (NENs), a non-negligible proportion (9-22%) is represented by sufferers of NENs of unknown primary origin (UPO), a poor prognostic group with largely unmet clinical needs. In the absence of standard therapeutic algorithms, current guidelines suggest that the treatment of UPO-NENs should be based on tumor clinical-pathological characteristics, disease burden, and patient conditions. Chemotherapy represents the backbone for the treatment of high-grade poorly differentiated UPO-NENs, usually providing deep but short-lasting responses. Conversely, the spectrum of available systemic therapy options for well-differentiated UPO-NENs may range from somatostatin analogs in indolent low-grade tumors, to peptide receptor radioligand therapy, tyrosine kinase inhibitors (TKIs), or chemotherapy for more aggressive tumors or in case of high disease burden. In recent years, molecular profiling has provided deep insights into the molecular landscape of UPO-NENs, with both diagnostic and therapeutic implications. Although preliminary, interesting activity data have been provided about upfront chemoimmunotherapy, the use of immune checkpoint inhibitors (ICIs), and the combination of ICIs plus TKIs in this setting. Here, we review the literature from the last 30 years to examine the available evidence about the treatment of UPO-NENs, with a particular focus on future perspectives, including the expanding scenario of targeted agents in this setting.
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Affiliation(s)
- Francesca Corti
- Medical Oncology Unit, Fondazione IRCCS San Gerardo dei Tintori, Via G.B. Pergolesi 33, 20900 Monza, Italy; (P.C.); (G.P.); (A.T.); (A.G.); (R.L.); (D.L.C.)
| | - Roberta Elisa Rossi
- Gastroenterology and Endoscopy Unit, IRCCS Humanitas Research Hospital, Via Manzoni 56, Rozzano, 20089 Milan, Italy;
| | - Pietro Cafaro
- Medical Oncology Unit, Fondazione IRCCS San Gerardo dei Tintori, Via G.B. Pergolesi 33, 20900 Monza, Italy; (P.C.); (G.P.); (A.T.); (A.G.); (R.L.); (D.L.C.)
| | - Gaia Passarella
- Medical Oncology Unit, Fondazione IRCCS San Gerardo dei Tintori, Via G.B. Pergolesi 33, 20900 Monza, Italy; (P.C.); (G.P.); (A.T.); (A.G.); (R.L.); (D.L.C.)
| | - Antonella Turla
- Medical Oncology Unit, Fondazione IRCCS San Gerardo dei Tintori, Via G.B. Pergolesi 33, 20900 Monza, Italy; (P.C.); (G.P.); (A.T.); (A.G.); (R.L.); (D.L.C.)
| | - Sara Pusceddu
- Gastro-Entero-Pancreatic and Neuroendocrine Unit 1, Department of Medical Oncology, ENETS Center of Excellence, Fondazione IRCCS Istituto Nazionale dei Tumori, Via Venezian 1, 20133 Milan, Italy; (S.P.); (S.O.)
| | - Jorgelina Coppa
- Hepatology and Hepato-Pancreatic-Biliary Surgery and Liver Transplantation Unit, Fondazione IRCCS, Istituto Nazionale Tumori, Via Venezian 1, 20133 Milan, Italy;
| | - Simone Oldani
- Gastro-Entero-Pancreatic and Neuroendocrine Unit 1, Department of Medical Oncology, ENETS Center of Excellence, Fondazione IRCCS Istituto Nazionale dei Tumori, Via Venezian 1, 20133 Milan, Italy; (S.P.); (S.O.)
| | - Alessandro Guidi
- Medical Oncology Unit, Fondazione IRCCS San Gerardo dei Tintori, Via G.B. Pergolesi 33, 20900 Monza, Italy; (P.C.); (G.P.); (A.T.); (A.G.); (R.L.); (D.L.C.)
| | - Raffaella Longarini
- Medical Oncology Unit, Fondazione IRCCS San Gerardo dei Tintori, Via G.B. Pergolesi 33, 20900 Monza, Italy; (P.C.); (G.P.); (A.T.); (A.G.); (R.L.); (D.L.C.)
| | - Diego Luigi Cortinovis
- Medical Oncology Unit, Fondazione IRCCS San Gerardo dei Tintori, Via G.B. Pergolesi 33, 20900 Monza, Italy; (P.C.); (G.P.); (A.T.); (A.G.); (R.L.); (D.L.C.)
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Moradi A, Lamsehchi N, Khaki S, Nasiri-Toosi M, Jafarian A. Liver Transplant for Patients With Neuroendocrine Tumor: A Report of 2 Exceptional Cases and Literature Review. EXP CLIN TRANSPLANT 2023; 21:578-585. [PMID: 37584538 DOI: 10.6002/ect.2023.0110] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 08/17/2023]
Abstract
Patients with neuroendocrine tumors with unresec-table liver involvement can benefit from liver transplant. There is a specific set of guidelines for neuroendocrine tumors with liver metastasis that involve less than 50% of the liver. However, beyond those guidelines, there are reports of exceptional criteria patients who benefited from liver transplant. Here, we present 2 unusual cases of patients with exceptional circumstances and with neuroendocrine tumors who underwent liver transplant. The first case describes a patient with an extremely rare neuroen-docrine tumor of the proximal common bile duct that caused liver biliary cirrhosis. The patient underwent tumor resection and liver transplant concurrently. The second case describes a patient with a neuroendocrine tumor of unknown primary origin with more than 50% hepatic involvement who received a liver transplant after downstaging. In our center, patients with unresectable hepatic metastases from neuroendoc-rine tumors are currently selected for liver transplant based on well-established criteria. However, these 2 cases did not meet the criteria for consideration of liver transplant; thus, multidisciplinary team sessions were held to discuss these 2 cases. After a period of nonsurgical treatment and evaluation of the tumor behavior, we selected the patients as candidates for liver transplant based on the favorable tumor behavior and favorable response to treatment. For both patients, we did not observe any signs of tumor recurrence during follow-up. The outcomes were acceptable, and the patients tolerated treatment well. Considering the favorable tumor pathology (G1 phase and low Ki67 index), we suggest that more studies should be conducted to evaluate the outcomes of patients with low-grade tumors and that the criteria for patients with low-grade tumors could be extended based on such future data.
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Affiliation(s)
- Alimohammad Moradi
- From the Department of General Surgery Division of Hepato-Pancreatico-Biliary Surgery and Organ Transplantation Surgery, Tehran University of Medical Sciences, Tehran, Iran
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Ilić D, Kunac N, Borčić T, Dinjar Kujundžić P, Mišetić Dolić Z, Sobočan N, Lalovac M, Mijić M, Međimurec G, Kocman B, Mikolašević I, Filipec Kanižaj T. Liver transplantation in patients with neuroendocrine tumors: a case series and literature review. Croat Med J 2021; 62:44-51. [PMID: 33660960 PMCID: PMC7976884 DOI: 10.3325/cmj.2021.62.44] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/10/2020] [Accepted: 02/05/2021] [Indexed: 12/02/2022] Open
Abstract
Neuroendocrine tumors (NET) are a rare and heterogeneous group of neoplasms with variable biological behavior. They frequently metastasize to the liver, requiring active, multimodality treatment. Surgical resection, possible in only a minority of cases, was until recently the only potentially curative option. For unresectable NET with liver metastases, liver transplantation (LT) emerged as a potential curative treatment due to relatively slow growth and indolent behavior of the metastases. In this case series with literature review, we retrospectively analyzed the characteristics of 12 highly selected patients with metastatic NET disease as an indication for LT treated in our center. We also summarized the proposed prognostic factors, and evaluated and compared the existing selection criteria. The main poor prognostic factors in our patients were high grade NET and primary tumor in the pancreas. Inconsistent liver transplantation outcome parameters make it difficult to standardize patient selection criteria. There is a need for further studies that would fully elucidate the curative potential of LT in patients diagnosed with NET.
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Affiliation(s)
- Diana Ilić
- Diana Ilić, UH Merkur, Zajčeva 19, 10000 Zagreb, Croatia,
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Fung AK, Chong CC. Surgical strategy for neuroendocrine liver metastases. SURGICAL PRACTICE 2019. [DOI: 10.1111/1744-1633.12364] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/26/2022]
Affiliation(s)
- Andrew Kai‐Yip Fung
- Department of SurgeryThe Chinese University of Hong Kong, Prince of Wales Hospital Hong Kong
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Xie R, Fu KI, Chen SM, Tuo BG, Wu HC. Neurofibromatosis type 1-associated multiple rectal neuroendocrine tumors: A case report and review of the literature. World J Gastroenterol 2018; 24:3806-3812. [PMID: 30197486 PMCID: PMC6127664 DOI: 10.3748/wjg.v24.i33.3806] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/17/2018] [Revised: 07/12/2018] [Accepted: 07/21/2018] [Indexed: 02/06/2023] Open
Abstract
Neurofibromatosis type 1 (NF-1) is commonly associated with benign or malignant tumors in both the central and peripheral nervous systems. However, rare cases of NF-1-associated multiple rectal neuroendocrine tumors have been reported. This report describes a case of a 39 year old female with NF-1 and intermittent hematochezia as a primary symptom. Physical examination showed multiple subcutaneous nodules and café au lait spots with obvious scoliosis of the back. Imaging examinations and colonoscopy found malformation of the left external iliac vein and multiple gray-yellow nodules with varying sizes and shapes in the rectal submucosal layer. Histological and immunohistochemical results suggested multiple rectal neuroendocrine tumors, a rare disease with few appreciable symptoms and a particularly poor prognosis. The patient with NF-1 presented here had not only multiple rectal neuroendocrine neoplasms but also vascular malformations, scoliosis and other multiple system lesions. This case therefore contributes to improving clinical understanding, diagnosis and treatment of related complications for patients with NF-1 who present with associated medical conditions.
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Affiliation(s)
- Rui Xie
- Department of Gastroenterology, Affiliated Hospital to Zunyi Medical College, Zunyi 563003, Guizhou Province, China
| | - Kuang-I Fu
- Department of Gastroenterology, Affiliated Hospital to Zunyi Medical College, Zunyi 563003, Guizhou Province, China
- Department of Endoscopy, Kanma Memorial Hospital, Tokyo 3250046, Japan
| | - Shao-Min Chen
- Department of Gastroenterology, Affiliated Hospital to Zunyi Medical College, Zunyi 563003, Guizhou Province, China
| | - Bi-Guang Tuo
- Department of Gastroenterology, Affiliated Hospital to Zunyi Medical College, Zunyi 563003, Guizhou Province, China
| | - Hui-Chao Wu
- Department of Gastroenterology, Affiliated Hospital to Zunyi Medical College, Zunyi 563003, Guizhou Province, China
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Moris D, Tsilimigras DI, Ntanasis-Stathopoulos I, Beal EW, Felekouras E, Vernadakis S, Fung JJ, Pawlik TM. Liver transplantation in patients with liver metastases from neuroendocrine tumors: A systematic review. Surgery 2017; 162:525-536. [PMID: 28624178 DOI: 10.1016/j.surg.2017.05.006] [Citation(s) in RCA: 103] [Impact Index Per Article: 12.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/02/2017] [Revised: 04/28/2017] [Accepted: 05/02/2017] [Indexed: 02/08/2023]
Abstract
BACKGROUND Liver transplantation to treat neuroendocrine tumors, especially in the setting of diffuse liver involvement not amenable to operative resection remains controversial. We sought to perform a systematic review of the current literature to summarize data on patients undergoing liver transplantation with neuroendocrine tumors liver metastases as the indication. METHODS A systematic review was conducted in accordance to the Preferred Reporting Items for Systematic reviews and Meta-Analysis guidelines. Eligible studies were identified using 3 distinct databases through March 2017: Medline (PubMed), ClinicalTrials.gov, and Cochrane library, Cochrane Central Register of Controlled Trials using a search algorithm: "(neuroendocrine or NET) and transplantation and liver." RESULTS From the 1,216 records retrieved, 64 studies were eligible. Overall, 4 studies presented data from registries, namely the European Liver Transplant Registry and the United Network for Organ Transplantation/Organ Procurement and Transplantation Network databases, 3 were multicenter studies. The largest cohort of data on patients undergoing liver transplantation for neuroendocrine tumors liver metastasis indication were from single center studies comprising a total of 279 patients. Pancreas was the primary tumor site for most patients followed by the ileum. Several studies reported that more than half of patients presented with synchronous disease (55.9% and 57.7%); in contrast, metachronous neuroendocrine tumors liver metastasis ranged from 17.7% to 38.7%. Overall, recurrence after liver transplantation ranged from 31.3% to 56.8%. Reported 1-, 3-, and 5-year overall survival was 89%, 69%, and 63%, respectively. Several prognostic factors associated with worse long-term survival including transplantation >50% liver tumor involvement, high Ki67, as well as a pancreatic neuroendocrine tumors versus gastrointestinal neuroendocrine tumors tumor location. CONCLUSION Liver transplantation may provide a survival benefit among patients with diffuse neuroendocrine tumors metastases to the liver. However, due to high recurrence rates, strict selection of patients is critical. Due to the scarcity of available grafts and the lack of level 1 evidence, the recommendations to endorse liver transplantation for extensive liver neuroendocrine tumors metastases warrants ongoing deliberations.
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Affiliation(s)
- Dimitrios Moris
- Department of Surgery, Division of Surgical Oncology, The Ohio State University Wexner Medical Center and James Cancer Hospital and Solove Research Institute, Columbus, OH
| | - Diamantis I Tsilimigras
- First Department of Surgery, Laikon General Hospital, School of Medicine, National and Kapodistrian University of Athens, Athens, Greece
| | - Ioannis Ntanasis-Stathopoulos
- First Department of Surgery, Laikon General Hospital, School of Medicine, National and Kapodistrian University of Athens, Athens, Greece
| | - Eliza W Beal
- Department of Surgery, Division of Surgical Oncology, The Ohio State University Wexner Medical Center and James Cancer Hospital and Solove Research Institute, Columbus, OH
| | - Evangelos Felekouras
- First Department of Surgery, Laikon General Hospital, School of Medicine, National and Kapodistrian University of Athens, Athens, Greece
| | - Spiridon Vernadakis
- Transplantation Unit, Laikon General Hospital, School of Medicine, National and Kapodistrian University of Athens, Athens, Greece
| | - John J Fung
- Department of Surgery, University of Chicago Medicine Transplant Institute, University of Chicago, Chicago, IL
| | - Timothy M Pawlik
- Department of Surgery, Division of Surgical Oncology, The Ohio State University Wexner Medical Center and James Cancer Hospital and Solove Research Institute, Columbus, OH.
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Yalcin S, Bayram F, Erdamar S, Kucuk O, Oruc N, Coker A. Gastroenteropancreatic neuroendocrine tumors: recommendations of Turkish multidisciplinary neuroendocrine tumor study group on diagnosis, treatment and follow-up. Arch Med Sci 2017; 13:271-282. [PMID: 28261279 PMCID: PMC5332464 DOI: 10.5114/aoms.2017.65449] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/12/2015] [Accepted: 05/20/2015] [Indexed: 02/06/2023] Open
Abstract
Gastroenteropancreatic neuroendocrine tumors (GEPNETs) are a relatively rare, heterogeneous group of diseases in which important advances have been observed in the diagnosis and treatment as well as in our understanding of the biology and genetics of the disease in recent years. Given the insufficient scientific data available on evidence-based management of GEPNETs and the differences in circumstances in individual countries, a multidisciplinary study group was established to provide guidelines for the management of GEPNETS. This study group consisted of a medical oncologist, endocrinologist, surgeon, pathologist, gastroenterologist, and a nuclear medicine specialist, who aimed to prepare a practical guide in the light of existing scientific data and international guidelines, to be used in common clinical practice.
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Affiliation(s)
- Suayib Yalcin
- Department of Medical Oncology, Institute of Cancer, Hacettepe University, Ankara, Turkey
| | - Fahri Bayram
- Department of Endocrinology, Erciyes University, Kayseri, Turkey
| | - Sibel Erdamar
- Department of Pathology, Cerrahpasa Medical School, Istanbul, Turkey
| | - Ozlem Kucuk
- Department of Nuclear Medicine, Ankara University, Ankara, Turkey
| | - Nevin Oruc
- Department of Gastroenterology, Ege University, Izmir, Turkey
| | - Ahmet Coker
- Department of Gastroenterology, Ege University, Izmir, Turkey
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Donor-Derived Hepatic Neuroendocrine Tumor: Pause Before Proceeding With Liver Retransplantation. Transplant Direct 2016; 2:e88. [PMID: 27830182 PMCID: PMC5087570 DOI: 10.1097/txd.0000000000000549] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/08/2015] [Revised: 09/22/2015] [Accepted: 09/24/2015] [Indexed: 02/06/2023] Open
Abstract
Gastrointestinal neuroendocrine tumors (NET) are rare but the age-adjusted incidence in the United States has increased, possibly due to improved radiographic and endoscopic detection. In advanced NET, hepatic metastases are common. Orthotopic liver transplant (OLT) is currently considered an acceptable therapy for selected patients with limited hepatic disease or liver metastases where complete resection is thought to have curative intent. The development of NET of donor origin is very uncommon after organ transplant, and it is unclear if the same treatment strategies applied to hepatic NET would also be efficacious after OLT. Here, we describe a unique case of an OLT recipient with a donor-derived NET that was treated with redo OLT as the primary therapy. The donor-derived NET recurred in the recipient's second liver allograft suggesting an extrahepatic reservoir. This case describes the natural history of such a rare event. Here, we highlight the treatment options for hepatic NET and challenge the role of OLT for a donor-derived hepatic NET.
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Acute thrombocytopenia: An uncommon complication occurring following transarterial chemoembolization in a patient with neuroendocrine hepatic metastases. Oncol Lett 2015; 10:247-249. [PMID: 26171007 DOI: 10.3892/ol.2015.3232] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/17/2014] [Accepted: 04/30/2015] [Indexed: 11/05/2022] Open
Abstract
Neuroendocrine tumors are a group of carcinomas that secrete various polypeptides with hormonal activity. A significant percentage of patients already have hepatic metastases at the time of initial diagnosis, and 80-90% of these tumors are inoperable at the time of presentation. Transarterial chemoembolization (TACE) is the preferred approach for the management of neuroendocrine hepatic metastases. Although the technique is relatively safe, it is associated with several complications. The present study reported the case of a patient with neuroendocrine hepatic metastases who developed acute thrombocytopenia following TACE. To the best of our knowledge, acute thrombocytopenia occurring after TACE in a patient with neuroendocrine hepatic metastases has not been previously reported. In the present study, the hypothetical etiopathogenetic mechanisms were also discussed.
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Ortiz J, Balasubramanian M, Brown T, Cetrulo L. Liver transplant for neuroendocrine tumor metastatic to the liver: literature review and report of extirpation at 16-year recurrence. EXP CLIN TRANSPLANT 2014; 13:86-91. [PMID: 25343464 DOI: 10.6002/ect.2013.0215] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/05/2022]
Abstract
New information has demonstrated that there are few long-term disease-free survivors after a liver transplant for neuroendocrine tumors. All studies have limited follow-up to 10 years after a transplant. We present the case of a recurrent metastatic carcinoid in a patient 16 years after an orthotopic liver transplant. The subject initially presented with worsening chronic diarrhea, hypoglycemia, and confusion with massive hepatomegaly. The postoperative pathology report showed 80% to 90% of the liver tissue replaced by biopsy-proven synaptophysin-positive intrahepatic tumor with neuroendocrine differentiation. At the time of his liver transplant, he also underwent a distal pancreatectomy and splenectomy. Nuclear medicine tumor location studies, ultrasound, and computed tomography studies were performed at regular yearly intervals for 8 years on follow-up. Sixteen years after his orthotopic liver transplant, a retroperitoneal mass was detected showing neuroendocrine differentiation. Older studies focusing on an orthotopic liver transplant for highlighted clinical features would positively predict long-term survival. Older studies found the following features to be predictive of long-term survival in liver transplant for neuroendocrine tumors: age < 55 years, < 50% replacement of liver with metastatic neoplastic tissue and carcinoid type. These features were identified on multiple studies as positive predictors of disease-free survival. These studies were limited to, at most, 10-year follow-up. Newer studies have examined molecular features such as expression of E-cadherin and Ki-67 as positive predictors of long-term survival. However, no study has determined the full natural history of these tumors and for how long these patients should be followed. This anecdotal report highlights that late recurrence can occur.
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Affiliation(s)
- Jorge Ortiz
- From the Division of Transplantation, University of Toledo Medical Center, USA
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Abstract
The aim of this study is to assess in bronchial carcinoid tumors, the prognostic factors in relation to the histology that would determine their most appropriate therapy. The histologic aggressiveness is a determining factor in tumor size and nodal involvement in these tumors. The knowledge of the histologic limits of typical and atypical carcinoid contributes to the recognition of a better valuation of the proportional significance that nodal involvement and histologic grade have in a tumor's prognosis.
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Del Prete M, Fiore F, Modica R, Marotta V, Marciello F, Ramundo V, Di Sarno A, Carratù A, di Roseto CDL, Tafuto S, Tatangelo F, Baldelli R, Colao A, Faggiano A. Hepatic arterial embolization in patients with neuroendocrine tumors. JOURNAL OF EXPERIMENTAL & CLINICAL CANCER RESEARCH : CR 2014; 33:43. [PMID: 24887262 PMCID: PMC4038067 DOI: 10.1186/1756-9966-33-43] [Citation(s) in RCA: 41] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Download PDF] [Subscribe] [Scholar Register] [Received: 03/06/2014] [Accepted: 05/05/2014] [Indexed: 12/23/2022]
Abstract
Liver metastases occur in 46-93% of patients with neuroendocrine neoplasms (NENs). Presence and extension of liver metastases are considered important prognostic factors, as they may significantly impair the patient's quality of life, because of either tumor bulk or hormonal hypersecretion. Therapies for NEN liver metastases include surgical resection, liver transplantation, chemotherapy and biotherapy. Surgery is the gold standard for curative therapy, but in most of NEN patients with liver metastases, when surgery can not be applied, minimally invasive therapeutic approaches are adopted. They include trans-arterial embolization (TAE), trans-arterial chemoembolization (TACE), radiofrequency thermal ablation and new emerging techniques.TAE is based on selective infusion of particles in the branch of the hepatic artery supplying the tumor lesions. The goal of TAE is to occlude tumor blood vessels resulting in ischemia and necrosis. Many reports have shown that TAE can reduce tumor size and hormone output, resulting in palliation of symptoms without the use of cytotoxic drugs, resulting in better tolerability. This review will focus on TAE performance and safety in NEN patients with liver metastases.
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Affiliation(s)
| | | | | | | | | | | | | | | | | | | | | | | | | | - Antongiulio Faggiano
- Divisione di Endocrinologia, Dipartimento di Medicina Clinica e Chirurgia, Università di Napoli Federico II, Naples, Italy.
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Rossi RE, Massironi S, Spampatti MP, Conte D, Ciafardini C, Cavalcoli F, Peracchi M. Treatment of liver metastases in patients with digestive neuroendocrine tumors. J Gastrointest Surg 2012; 16:1981-1992. [PMID: 22829240 DOI: 10.1007/s11605-012-1951-1] [Citation(s) in RCA: 12] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/13/2012] [Accepted: 06/24/2012] [Indexed: 02/05/2023]
Abstract
BACKGROUND Liver metastases are a strong prognostic indicator in patients with gastro-entero-pancreatic neuroendocrine tumors (GEP-NETs). Therapeutic options for metastatic NETs are expanding and not mutually exclusive. AIMS This paper reviews the literature relating to multidisciplinary approach towards GEP-NET metastases, to highlight advances in knowledge regarding these tumors, and to understand the interdisciplinary management of individual patients. METHODS A PubMed search was performed for English-language publications from 1995 through 2012. Reference lists from studies selected were manually searched to identify further relevant reports. Manuscripts comparing different therapeutic options and advances for GEP-NET-related liver metastases were selected. RESULTS There is considerable controversy regarding the optimal management of GEP-NET metastases. Although radical surgery still remains the gold standard, a variety of other therapeutic options are available for metastatic GEP-NETs, including loco-regional chemotherapy/radiotherapy, radioembolization, systemic peptide receptor radionuclide therapy, biotherapy, and chemotherapy. In selected patients, liver transplantation should also be considered. Systemic somatostatin analogues and/or interferon show anti-proliferative effects, representing an appropriate first-line treatment for most patients. In advanced metastatic NETs, recent options include targeted therapies (i.e., everolimus and sunitinib). CONCLUSIONS It is evident that multidisciplinary care and multimodality treatments remain the cornerstone of management of NET patients. Since NETs often show a more indolent behavior compared to other malignancies, physicians should aim to preserve a satisfactory quality of life for the patient by personalizing the therapeutic approach according to the tumor's features and prognostic factors.
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Affiliation(s)
- Roberta Elisa Rossi
- Postgraduate School of Gastroenterology, Università degli Studi di Milano, Milan, Italy.
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Surgical treatment of liver metastases in neuroendocrine neoplasms. Int J Hepatol 2012; 2012:782672. [PMID: 22319653 PMCID: PMC3272813 DOI: 10.1155/2012/782672] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/15/2011] [Accepted: 10/07/2011] [Indexed: 12/15/2022] Open
Abstract
Neuroendocrine neoplasms (NENs) are a distinctive entity, and nearly 10% of patients already have liver metastases at presentation. The management of neuroendocrine liver metastases (NEN-LM) is complex with differing patterns of metastatic presentation. An aggressive approach should be used to resect the primary tumor, to remove regional lymph nodes, and to resect or treat appropriate distant metastases (including liver tumors). Despite having an indolent course, NENs have a significantly reduced survival when liver metastases are untreated. Though a wide range of therapies are now available with a multimodal approach to the treatment, surgical treatment offers the only chance for a significant survival prolongation and/or improvement of symptoms and quality of life. A review of the existing surgical modalities for NEN-LM is discussed in this paper.
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A multimodal approach to the management of neuroendocrine tumour liver metastases. Int J Hepatol 2012; 2012:819193. [PMID: 22518323 PMCID: PMC3296190 DOI: 10.1155/2012/819193] [Citation(s) in RCA: 26] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/03/2011] [Accepted: 12/02/2011] [Indexed: 12/13/2022] Open
Abstract
Neuroendocrine tumours (NETs) are often indolent malignancies that commonly present with metastatic disease in the liver. Surgical, locoregional, and systemic treatment modalities are reviewed. A multidisciplinary approach to patient care is suggested to ensure all therapeutic options explored.
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Khan MS, Caplin ME. Therapeutic management of patients with gastroenteropancreatic neuroendocrine tumours. Endocr Relat Cancer 2011; 18 Suppl 1:S53-74. [PMID: 22005115 DOI: 10.1530/erc-10-0271] [Citation(s) in RCA: 16] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/22/2022]
Abstract
Patients with neuroendocrine tumours (NETs) are best managed in a specialist centre as part of a multidisciplinary team comprising gastroenterologists, oncologists, endocrinologists, gastrointestinal and hepatopancreaticobiliary surgeons, pathologists, nuclear medicine physicians and technicians, radiologists, specialist nurses, pharmacists, biochemists and dieticians. This should ideally be led by a clinician with experience and interest in NETs. Although the number of medical treatments and clinical trials has increased in the decade, there is still a lack of prospective randomised trials; thus, management is mainly based on limited often single-centre studies, although there are now formal guidelines based on consensus expert opinion. We have outlined the current optimal management of patients with NETs. We have reviewed therapeutic options including surgery, somatostatin analogues and other biotherapies and peptide receptor-targeted therapy. We have discussed the challenge in managing hepatic metastases including hepatic artery embolisation, ablation and orthotopic liver transplant. In addition, we have briefly reviewed the emerging therapies such as the mammalian target of rapamycin and angiogenic inhibitors and the newer somatostatin analogues.
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Affiliation(s)
- Mohid S Khan
- Neuroendocrine Tumour Unit, Centre for Gastroenterology, Royal Free Hospital, London NW3 2QG, UK
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Karabulut K, Akyildiz HY, Lance C, Aucejo F, McLennan G, Agcaoglu O, Siperstein A, Berber E. Multimodality treatment of neuroendocrine liver metastases. Surgery 2011; 150:316-25. [PMID: 21801968 DOI: 10.1016/j.surg.2011.05.008] [Citation(s) in RCA: 36] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/19/2010] [Accepted: 05/12/2011] [Indexed: 01/29/2023]
Abstract
BACKGROUND Neuroendocrine liver metastases have a distinct tumor biology and symptomatology that render their management challenging. This difficulty is reflected in the literature, which lacks consensus on a treatment algorithm. The aim of this study is to propose a treatment algorithm based on patient morbidity and the efficacy of different treatment options. METHODS The medical records of 127 patients with neuroendocrine liver metastases were reviewed. As first-line treatment, 69 of these patients underwent radiofrequency ablation (RFA), 29 patients were treated by liver resection, and 29 underwent embolization. Clinical characteristics and surgical parameters were analyzed with the chi-square test, and cumulative survival was analyzed with the Kaplan-Meier method. All data are expressed as mean ± standard error of the mean. RESULTS Of the 3 treatment modalities, RFA was the most commonly used initial treatment for patients with up to approximately 16 discrete lesions. Resection was used to debulk large tumors of limited number. Embolization was the first-line treatment for more extensive disease not amenable to RFA or resection. RFA provided effective cytoreduction while affording patients a shorter duration of stay and lower complication rates. On univariate analysis, the size of dominant metastases, extrahepatic disease, resection of primary tumor, and treatment modality affected survival. On multivariate analysis, sex, the size of dominant metastases, and extrahepatic disease were independent predictors of survival. CONCLUSION To our knowledge, this study is the largest report on a multimodality approach to the treatment of neuroendocrine liver metastases yet published in the literature. Because of the patient selection criteria used in our study, a direct comparison of the treatment arms is not strictly possible. We used an initial treatment algorithm based on the presentation of the patient. Because this disease has a multifocal nature and accompanying elevated recurrence rate, careful follow-up of patients and subsequent treatments are often needed to minimize disease burden.
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Affiliation(s)
- Koray Karabulut
- Liver Tumor Ablation Program, Endocrinology and Metabolism Institute, Cleveland Clinic, Cleveland, OH, USA
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Takagawa R, Tanaka K, Yamada M, Nojiri K, Kumamoto T, Ueda M, Endo I. Primary neuroendocrine carcinoma of the hypopharynx: a case report. Dis Esophagus 2011; 24:E26-31. [PMID: 21438964 DOI: 10.1111/j.1442-2050.2011.01191.x] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
Primary neuroendocrine carcinoma of the hypopharynx is extremely rare. A 59-year-old man complaining of swollen right cervical lymph node was admitted to our hospital. Although computed tomography, upper endoscopy, and positron emission tomography scan were performed, the primary lesion was unknown. Bilateral neck lymph node dissection was performed and diagnosed as metastasis of neuroendocrine carcinoma. Sixteen months after the first operation, computed tomography scan revealed multiple liver metastases. There was no another metastatic lesion, and hepatectomy with negative margin was performed. Three months after the second operation, a small tumor of the hypopharynx was detected by upper endoscopy, and biopsy revealed neuroendocrine carcinoma. Concurrent chemotherapy (cisplatin + docetaxel) and radiotherapy (60 Gy) were carried out. This therapy was highly effective, and primary lesion disappeared. After the chemoradiotherapy, lung metastasis and bone metastasis emerged and treated by radiotherapy and chemotherapy (cisplatin + irinotecan). These therapies were also effective, but multiple liver metastases appeared. The patient died 39 months after the first surgery. Although neuroendocrine carcinoma is a high-grade malignancy which metastasizes easily, combined treatment strategy may be useful for these patients. We have here reported, with bibliographic consideration, a case in which multimodal treatment was employed for primary hypopharyngeal neuroendocrine carcinoma with distant metastases.
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Affiliation(s)
- R Takagawa
- Department of Gastroenterological Surgery, Graduate School of Medicine, Yokohama City University, Yokohama, Japan.
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Nguyen NTT, Harring TR, Goss JA, O'Mahony CA. Neuroendocrine Liver Metastases and Orthotopic Liver Transplantation: The US Experience. Int J Hepatol 2011; 2011:742890. [PMID: 22254141 PMCID: PMC3255281 DOI: 10.4061/2011/742890] [Citation(s) in RCA: 49] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/02/2011] [Revised: 09/30/2011] [Accepted: 10/01/2011] [Indexed: 12/14/2022] Open
Abstract
Liver transplantation remains a controversial therapy for Neuroendocrine liver metastases (NLM), with coflicting suvival data reported. The aim was to assess the evolution of outcomes for patients transplanted for NLM in the US, both before and after the introduction of the MELD scoring system in 2002. The UNOS/OPTN database was reviewed to identify patients diagnosed with NLM who subsequently underwent a liver transplantation from 1988 to March 2011 (n = 184); Patient survival was determined using Kaplan-Meier methods and log-rank tests, and cox regression analysis was performed, using SPSS 15.0 (SPSS, Inc, Chicago, IL). The overall NLM patient survivals in the pre-MELD era were 79.5%, 61.4%, and 49.2% at 1, 3, and 5 years, respectively. After the introduction of the MELD score, NET/NLM patients had improved overall patient survivals at 1, 3, and 5 years of 84.7%, 65%, and 57.8%. Patients transplanted after 2002 had an improved survival outcome. Notably, the overall patient survival for NET is not significantly different when compared to the outcomes of patients transplanted for HCC, in the current era. This progress acknowleges the significant improvement in outcomes for NLM patients after liver transplantation and the potential for further gain in the survival of otherwise nonsurgical, terminal patients.
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Affiliation(s)
- N. Thao T. Nguyen
- Division of Abdominal Transplantation and Hepatobiliary Surgery, Michael E. DeBakey Department of Surgery, Baylor College of Medicine, 1709 Dryden Road, Suite 1500, Houston, Tx 77030, USA
| | - Theresa R. Harring
- Division of Abdominal Transplantation and Hepatobiliary Surgery, Michael E. DeBakey Department of Surgery, Baylor College of Medicine, 1709 Dryden Road, Suite 1500, Houston, Tx 77030, USA
| | - John A. Goss
- Division of Abdominal Transplantation and Hepatobiliary Surgery, Michael E. DeBakey Department of Surgery, Baylor College of Medicine, 1709 Dryden Road, Suite 1500, Houston, Tx 77030, USA
| | - Christine A. O'Mahony
- Division of Abdominal Transplantation and Hepatobiliary Surgery, Michael E. DeBakey Department of Surgery, Baylor College of Medicine, 1709 Dryden Road, Suite 1500, Houston, Tx 77030, USA,*Christine A. O'Mahony:
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Frilling A, Sotiropoulos GC, Li J, Kornasiewicz O, Plöckinger U. Multimodal management of neuroendocrine liver metastases. HPB (Oxford) 2010; 12:361-79. [PMID: 20662787 PMCID: PMC3028577 DOI: 10.1111/j.1477-2574.2010.00175.x] [Citation(s) in RCA: 105] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
BACKGROUND The incidence of neuroendocrine tumours (NET) has increased over the past three decades. Hepatic metastases which occur in up to 75% of NET patients significantly worsen their prognosis. New imaging techniques with increasing sensitivity enabling tumour detection at an early stage have been developed. The treatment encompasses a panel of surgical and non-surgical modalities. METHODS This article reviews the published literature related to management of hepatic neuroendocrine metastases. RESULTS Abdominal computer tomography, magnetic resonance tomography and somatostatin receptor scintigraphy are widely accepted imaging modalities. Hepatic resection is the only potentially curative treatment. Liver transplantation is justified in highly selected patients. Liver-directed interventional techniques and locally ablative measures offer effective palliation. Promising novel therapeutic options offering targeted approaches are under evaluation. CONCLUSIONS The treatment of neuroendocrine liver metastases still needs to be standardized. Management in centres of expertise should be strongly encouraged in order to enable a multidisciplinary approach and personalized treatment. Development of molecular prognostic factors to select treatment according to patient risk should be attempted.
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Affiliation(s)
- Andrea Frilling
- Department of Surgery and Cancer, Imperial College London, Hammersmith HospitalLondon, UK
| | | | - Jun Li
- Department of General, Visceral and Transplantation Surgery, University Hospital TübingenTübingen
| | - Oskar Kornasiewicz
- Department of Surgery and Cancer, Imperial College London, Hammersmith HospitalLondon, UK
| | - Ursula Plöckinger
- Interdisciplinary Centre for Metabolism: Endocrinology, Diabetes and Metabolism, Campus Virchow-Klinikum, Charité-Universitaetsmedizin BerlinBerlin, Germany
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Boleslawski E, Dharancy S, Truant S, Pruvot FR. Surgical management of liver metastases from gastrointestinal endocrine tumors. ACTA ACUST UNITED AC 2010; 34:274-82. [PMID: 20347242 DOI: 10.1016/j.gcb.2010.02.001] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/03/2009] [Revised: 01/27/2010] [Accepted: 02/02/2010] [Indexed: 02/07/2023]
Abstract
Liver metastases from endocrine tumors can reduce 5-year survival from 90% to 40% and, in cases of functional gastrointestinal endocrine tumors, lead to a carcinoid syndrome. Complete resection of cancerous disease should be considered in all cases. Indeed, after hepatectomy, prolonged survival (41-86% at five years) can be achieved, with low rates of surgery-related mortality (0-6.7%). Extended liver resection is required in most cases. Percutaneous portal embolization increases the volumetric feasibility of resection, and sequential hepatectomy techniques enable a two-stage resection of both bilobar metastases and the primary tumor. For carcinoid syndrome that does not respond to medical therapy, incomplete resection of liver metastases, by reducing tumor volume, may be indicated to reduce symptoms and halt the progression of carcinoid heart disease. In cases of non-resectable liver metastases in selected patients, liver transplantation can lead to 5-year survival rates as high as 77%.
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Affiliation(s)
- E Boleslawski
- Service de Chirurgie Digestive et de Transplantation, Hôpital Huriez, CHRU de Lille, rue Michel-Polonovski, 59037 Lille cedex, France.
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Kondo T, Matsuyama R, Ashihara H, Matsuo Y, Sasaki K, Goto R, Ono K, Takaki Y, Honda Y, Iyama KI, Kawashima J, Motoshima H, Tsuruzoe K, Miyamura N, Araki E. A case of ectopic adrenocorticotropic hormone-producing pancreatic neuroendocrine tumor with multiple liver metastases. Endocr J 2010; 57:229-36. [PMID: 20032567 DOI: 10.1507/endocrj.k09e-179] [Citation(s) in RCA: 21] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/23/2022] Open
Abstract
Ectopic adrenocorticotropic hormone (ACTH) production by the pancreatic neuroendocrine tumor (p-NET) is relatively rare, and patients with this tumor show poor prognosis. In this study, we present the case of a 64-year-old woman who presented with ectopic ACTH syndrome due to p-NET with multiple liver metastases. Computed tomography revealed that she had multiple masses in the liver and a solid mass in the head of the pancreas. Endocrinological examinations revealed markedly elevated plasma ACTH (735.0 pg/mL) and cortisol (34.7 microg/dL) levels associated with hypokalemia (2.7 mEq/L), diabetes and typical Cushingoid features. Histological examinations by needle biopsy of liver tumors in S5 and S8 indicated metastatic ACTH-producing NET, which was also confirmed by venous sampling. The metastatic live tumor was somatostatin receptor (SSTR)-2a- and SSTR-5-positive as revealed by immunohistochemical staining, and reverse transcription polymerase chain reaction revealed divergent expression patterns of SSTRs, pro-opiomelanocortin, and gastrin mRNA. To avoid complications of hypercortisolemia, metyrapone was first administered to reduce the cortisol levels. After near-normalization of cortisol levels, transarterial chemoembolization and somatostatin analogue treatment were performed. The combination of these treatments effectively decreased ACTH and cortisol levels and also ameliorated hyperglycemia. We have achieved controlled hormone secretion and prevented tumor growth in this patient for more than 20 months, suggesting that highly individualized treatment for NET should be undertaken because of its divergent and heterogeneous characteristics.
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Affiliation(s)
- Tatsuya Kondo
- Department of Metabolic Medicine, Faculty of Life Sciences, Kumamoto University, Kumamoto, Japan
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Poggi G, Villani L, Bernardo G. Multimodality treatment of unresectable hepatic metastases from pancreatic glucagonoma. Rare Tumors 2009; 1:e6. [PMID: 21139900 PMCID: PMC2994425 DOI: 10.4081/rt.2009.e6] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/15/2009] [Accepted: 06/29/2009] [Indexed: 11/22/2022] Open
Abstract
Glucagonomas are pancreatic islet cell tumors arising from the alpha cells which belong to neuroendocrine tumors. They frequently metastasize to the liver. We report the case of a 52- year old man with a pancreatic glucagonoma with synchronous multiple liver metastases treated by surgery, transarterial chemoembolization, percutaneous radiofrequency thermal ablation and long-acting octreotide. Our report confirms that a multimodal approach is very effective in patients with unresectable liver metastases from pancreatic endocrine tumors providing long-lasting palliation and probably prolonging survival.
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Vogl TJ, Naguib NNN, Zangos S, Eichler K, Hedayati A, Nour-Eldin NEA. Liver metastases of neuroendocrine carcinomas: interventional treatment via transarterial embolization, chemoembolization and thermal ablation. Eur J Radiol 2008; 72:517-28. [PMID: 18829195 DOI: 10.1016/j.ejrad.2008.08.008] [Citation(s) in RCA: 119] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/10/2008] [Revised: 08/08/2008] [Accepted: 08/11/2008] [Indexed: 12/14/2022]
Abstract
UNLABELLED The aim of this review article is to provide a practical clinical guideline for indication, technical aspects, protocol guideline and strategies for the interventional treatment of liver metastases from neuroendocrine tumors and focusing on the results of various protocols of management. The response to therapy, in the published articles, is calculated on the basis of the following clinical parameters; including symptomatic response (SR), biologic response (BR), morphological response (MR), progress free survival (PFS), and survival periods (SP). Transarterial chemoembolization (TACE) has been associated with SR rates of 60-95%, BR of 50-90%, MR of 33-80%, SR of 20-80 months, and a 5-year survival of between 50% and 65%. PFS was also between 18 and 24 months. In the transarterial embolization (TAE) group, SR was similar to the TACE group, MR was 32% and 82%, survival was between 18 and 88 months with a survival rate of 40-67%, and BR was between 50% and 69%. Radiofrequency ablation (RFA), either percutaneous or during surgery, has been associated with SR of 71-95% for a mean duration of 8-10 months, BR of 65%, and mean SP of 1.6 years after ablation. The mean survival following surgical resection for operable cases is 4.26 years+/-S.D.: 1.1. CONCLUSION The interventional protocols for the management of liver metastases from neuroendocrine tumors: for oligonodular liver metastatic deposits, local resection or RFA and/or LITT is recommended, while in multinodular diseases with higher tumor load, TACE or TAE is recommended.
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Affiliation(s)
- Thomas J Vogl
- Institute for Diagnostic and Interventional Radiology, Johann Wolfgang Goethe - University Hospital, Theodor-Stern-Kai 7, 60590 Frankfurt am Main, Germany.
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Vasoactive intestinal polypeptide secreting pancreatic tumour with hepatic metastases: long term survival after orthotopic liver transplantation. Ir J Med Sci 2008; 179:439-41. [DOI: 10.1007/s11845-008-0209-0] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/18/2008] [Accepted: 07/21/2008] [Indexed: 10/21/2022]
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Le Treut YP, Grégoire E, Belghiti J, Boillot O, Soubrane O, Mantion G, Cherqui D, Castaing D, Ruszniewski P, Wolf P, Paye F, Salame E, Muscari F, Pruvot FR, Baulieux J. Predictors of long-term survival after liver transplantation for metastatic endocrine tumors: an 85-case French multicentric report. Am J Transplant 2008; 8:1205-13. [PMID: 18444921 DOI: 10.1111/j.1600-6143.2008.02233.x] [Citation(s) in RCA: 108] [Impact Index Per Article: 6.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/25/2023]
Abstract
Liver transplantation (LTx) for metastatic endocrine tumors (MET) remains controversial due to the lack of clear selection criteria. From 1989 to 2005, 85 patients underwent LTx for MET. The primary tumor was located in the pancreas or duodenum in 40 cases, digestive tract in 26 and bronchial tree in five. In the remaining 14 cases, primary location was undetermined at the time of LTx. Hepatomegaly (explanted liver > or =120% of estimated standard liver volume) was observed in 53 patients (62%). Extrahepatic resection was performed concomitantly with LTx in 34 patients (40%), including upper abdominal exenteration (UAE) in seven. Postoperative in-hospital mortality was 14%. Overall 5-year survival was 47%. Independent factors of poor prognosis according to multivariate analysis included UAE (relative risk (RR): 3.72), primary tumor in duodenum or pancreas (RR: 2.94) and hepatomegaly (RR: 2.63). After exclusion of cases involving concomitant UAE, the other two factors were combined into a risk model. Five-year survival rate was 12% for the 23 patients presenting both unfavorable prognostic factors versus 68% for the 55 patients presenting one or neither factor (p < 10(-7)). LTx can benefit selected patients with nonresectable MET. Patients presenting duodeno-pancreatic MET in association with hepatomegaly are poor indications for LTx.
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Affiliation(s)
- Y P Le Treut
- Department of Surgery, Hôpital La Conception, Marseille, France.
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Mazzaferro V, Pulvirenti A, Coppa J. Neuroendocrine tumors metastatic to the liver: how to select patients for liver transplantation? J Hepatol 2007; 47:460-6. [PMID: 17697723 DOI: 10.1016/j.jhep.2007.07.004] [Citation(s) in RCA: 206] [Impact Index Per Article: 11.4] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Affiliation(s)
- Vincenzo Mazzaferro
- Gastrointestinal Surgery and Liver Transplantation Unit, National Cancer Institute, Istituto Nazionale Tumori Fondazione IRCCS, Via Venezian 1, Milan 20133, Italy.
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Abstract
In summary, neuroendocrine tumors of the pancreas comprise a unique and relatively rare group of tumors, of which gastrinoma and insulinoma are the most common types. Insulinomas tend to be small, solitary and benign, with surgical resection curable in most cases. The remainder of the neuroendocrine tumors are usually large, and unlikely to be cured with surgery; their slow-growing nature, however, mandates aggressive surgical therapy; even in cases where metastatic disease is present. Somatostatin analogs such as octreotide, are used to control the symptoms of hormone secretion; they are generally less effective in patients with insulinoma than in those with the other neuroendocrine tumors. Streptozocin, 5-fluorouracil, and doxorubicin are the most widely used chemotherapeutic agents in metastatic neuroendocrine tumors; their efficacy is limited, and significant side effects limit their use. Finally, liver transplantation in very select patients may prolong survival and alleviate debilitating symptoms.
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Affiliation(s)
- Antonia E Stephen
- Department of Surgery, Massachusetts General Hospital, 55 Fruit Street, Boston, MA 02114, USA.
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Niederhuber JE, Fojo T. Treatment of Metastatic Disease in Patients with Neuroendocrine Tumors. Surg Oncol Clin N Am 2006; 15:511-33, viii. [PMID: 16882495 DOI: 10.1016/j.soc.2006.05.004] [Citation(s) in RCA: 11] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/23/2022]
Abstract
Gastroenteropancreatic neuroendocrine tumors (GENTs) compromise a heterogeneous group of relatively uncommon neoplasms with a yearly incidence rate of 1.2 to 3.0 per 100,000 population. These tumors share numerous histologic and biologic features, allowing their consideration as a common entity. They are postulated to arise from neuroendocrine cells, but most are not from neural crest origin. Their predominant site of origin is the gastrointestinal tract, where most involve the small intestine and appendix, but are also found in the adrenal medulla, bronchopulmonary system, pancreas, thyroid, parathyroid, and paraganglia cells. A common feature is their often indolent course, but some tumors are poorly differentiated and behave aggressively. This article addresses the surgical management of endocrine malignancies and the treatment of metastatic disease in patients with neuroendocrine tumors.
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Affiliation(s)
- John E Niederhuber
- National Cancer Institute, 31 Center Drive, Room 11A48, Bethesda, MD 20892, USA.
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